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Human immunodeficiency virus type 1 (HIV-1) proviral DNA is the double-stranded DNA intermediate formed after reverse transcription of the viral RNA genome, which is subsequently integrated into the host cell's nuclear DNA. This integrated provirus serves as the template for the production of new viral particles and is the fundamental basis for lifelong infection, as it persists in a latent state within resting CD4+ T cells despite suppressive antiretroviral therapy (ART) (NIH, 2023). Targeting specific protospacer sites within the proviral DNA using gene-editing tools like CRISPR-Cas9 allows for the precise excision or inactivation of the viral genome (Excision BioTherapeutics, 2024). These therapeutic interventions typically target highly conserved regions, such as the Long Terminal Repeats (LTRs) or the gag gene, to ensure broad coverage across viral variants and prevent the emergence of escape mutants (PubMed, PMID: 31406344). By permanently removing or disabling the provirus, these strategies aim to achieve a functional cure or long-term remission for individuals living with HIV (Nature Communications, 2019). This approach represents a shift from lifelong viral suppression to the potential elimination of the viral reservoir from the human body.
Site-specific DNA cleavage and excision of integrated viral DNA using CRISPR-Cas9 to permanently disrupt the replication-competent reservoir.
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